Alpha-hydroxy, beta-amino-propion-aldehyde



United States Patent nation of areas and materials and can readily be applied 75 2 as the active ingredient in solutions, emulsions andsus ALPHA-HYDROXY, BETA-AMlNO-PROPI'ON- ALDEHYDE John B. Wright and Edward H. Lincoln, Kalamazoo Township, Kalamazoo County, Mich., assignors to The Upjohn Company, Kalamazoo, Mich., a corporation of Michigan No Drawing. Application April 30, 1956 Serial No. 581,273

Claims. (Cl. 260-584) The present invention relates to novel fiamino-d-hydroxyalkanal acid addition compounds of the formula Ice Patented Feb. a4, 1959 pensions for spraying, washing, painting, immersing, etc, dusts, aerosols, fumigants, etc., according'to methods and procedures well known in the pesticide and disinfectant arts. As illustrated in Example 12, the" acid addition compounds of the present invention are more stable and have greater water solubility than the parent free base compounds, and, therefore, said acid addition compounds can be applied much more effectively and economically for the above uses. tion, and uses of the apparent to one skilled in the art.

Efiicacy of the present antiviral compounds is xillustrated by Table I which shows the typically superior results afforded by representative compounds in the'wellknown in ovo survival test forantiviral potency, em.- I I ploying Newcastles virus (NJ-KD strain) and influenza fl formyl flhydmxy aower alkyleneklffix A virus (PR8 strain) as illustrative viruses. In the test method used to obtain the data in Table I the particular wherein R is selected from the group consisting of hytest compound is dissolved in water or suspended in drogen and alkyl, R is selected from the group consistwater-carboxymethyl cellulose, depending on the degree ing of alkyl and fiformyl-fi hydroxy-(lower-alkylene), of water solubility. A known volume of such a solution lower-alkylene contains from two to five carbon atoms, or suspension containing a known concentration ofthe inclusive, (i. e. -C,,H wherein n is two to five, intest compound is injected into the allantoic sac of ten clusive), alkyl contains from one to eight carbon atoms, day fertile eggs, using the technique described by inclusive, and HX is an acid having a pK value less Beveridge and Burnet, Medical Research Council, Special than five. Of particular interest are the /8 -monoand Report Series No. 256, The Cultivation of Viruses and dia1kylamin0-whydroxypropionaldehyde mlneral acid Rickettsiae in the Chick Embryo, London, His Majestys addition compounds of the formulas 3 Stationery Office, 1946. The test compound is usually 0 OH H O OH alkyl administered at or slightly less than-the maximum tol- II I I I II I I erated dose, i. e., the greatest amount which when simi- HC 0H GH" N'mmm1aid HC 'CHOH2 lFmmemlac1d larly administered is found to cause no deaths in similar fllkyl alkyl eggs during a 216-hour incubation period. The same- TABLE I Test Compound Protective Index Milli New- Influ- Formula grams eastleas enzaA per egg Virus Virus C HPNH-CHQCHOHOHO-HCI 8.0 nO4H9NH-CHz-OHOH-OHO-HOI 4.0 onam-oni-onon-cno-nol 8 (0 HmNOHz-OHOH-OHO-H(Jl S 8 (G2H5) aNCH2-CHOHCH 0-H C1 (as dimer) 10. (1 I iso-osrn)2N0Hr0H0H0H0-H01 3. (mo-Cali?)zN-GHa-CHOH-OHOHOI (as d1iner) (II-0 H)z2NCHz-CHOH-CHO-HC] (as dimer). 8: 0 CHQ N(OHT-OHOH CHO)THOI 10.0

wherein alkyl contains from one to eight carbon atoms,

volume of the same menstruum without test compound is injected into similar eggs as a control. About fifteen minutes later all eggs, test and control, are inoculated with a virus suspension containing approximately fifty times the LD dosage of virus; one LD is that amount which kills fifty percent of virus-infected embryonated 0 OH H II I I eggs. The eggs are incubated at 37 degrees centigrade. acid Survivorship is determined by candling the eggs at eightow a1 y1 hour intervals during a 216-hour period. The protection 0 OH lower alkyl afiorded by a test compound is conveniently expressed 6 thus: percent survrvorship of treated eggs after 216 hours 39- II-OHrNmydmhflucacid (e. g. ninety percent) minus percent survivorship of lower-alkyl control eggs after 216 hours (e. g. five percent) equals the protective index (e. g. the maximum protective index value being 100. The test compounds listed in Table I, therefore, are highly potent antiviral agents.

The acid addition compounds of the present invention are prepared by reaction of the parent free base orjpref I erably a derivative thereof, e. g. an acetal, preferably the.

Other objects of the present invn-' novel compounds thereof, will be diethyl acetal, with an acid. Suitable acids are hydrochloric acid (especially preferred) hydrobromic acid and other hydrohalic acid, sulfuric acid, phosphoric acid, and other mineral acid, acetic acid, formic acid, benzoic acid, trichloroacetic acid, succinic acid, maleic acid, citrieaeid, tartaric acid, phenylacetic acid, oxali aid, furoic acid, 06- and fl-cyclopentylpropionic acid, a and fl-phenylpropionic acid, and other acid having a pK, value below five, the pK,, value being a common measure ofacid strength (Moeller, Inorganic Chemistry, John .Wiley and Sons, Incorporated, New York, New York,

1952, pages 313-315). The starting p-amino-a-hydroxyalkanals or preferably a derivative thereof, e. g. an acetal, preferably the diethyl acetal, are prepared by reaction of a primary or secondary alkylamine with an on, fl-epoxyalkanal or preferably a derivative thereof, e. g. an acetal, preferably the diethyl acetal, which epoxy compound 'in turn is prepared fromthe corresponding a, p-alkenal or derivative thereof, e. g an acetal, preferably the diethyl acetal. These reactions can be illustrated, using the preferred diethyl acetal derivative, by the equation --(|J=CCH(OC2H5)2 1 i :-'-n-c.n oc,nm -N- :o.n oo2nl). The following examples are illustrative only and are not to be construed as limiting the scope of the invention.

Example 1 To a solution of 410 grams of '33 percent aqueous ethylamine solution (approximately three moles) and 100 milliliters of methanol is added 146 grams (one'mole) of ufi-epoxypropionaldehyde diethylacetal during a period of about five minutes. An exothermic reaction takes place and the solution warms to fifty degrees centigrade and is prevented from going above this temperature by occasional cooling in a water bath. The solution is allowed to stand overnight and then heated under reflux for one hour and concentrated under reduced pressure on a steam bath using a six-inch Vigreux column. The solid residue is distilled under reduced pressure using a seven-inch column packed with glass helices. There is obtained 150.6 grams (79 percent) of a colorless liquid,

boiling at 117-119 degrees centigrade at thirteen milli- I meters pressure, which solidifies in'the condenser to a white solid; melting point 54.5-55.5 degrees .centigrade. Recrystallization from Skellysolve B (mixture of hexanes) gives colorless asbestos-like needles of fl-ethylamino-a-hydroxypropionaldehyde diethylacetal' of the same melting point.

Anal.-'Calcd. for C H NO C, 56.51; H, 11.07; N, 7.52. Found: C, 56.82; H, 10.97; N, 7.58.

To 48.8 grams (0.256 mole) of the B-ethylamino-ahydroxypropionaldehyde diethylacetal is added 42.4 milliliters 0.512 mole) of concentrated hydrochloric acid in 53 milliliters of water. The solution is warmed to 85 degrees centigrade during a period of about fifteen minutes and then maintained at room temperature for three days. The yellow solution then is concentrated under reduced pressure on a water bath at forty degrees centigrade and the solid residue is dried in a vacuum .desiccator over concentrated sulfuric acid and then over potassium hydroxide. The resulting solid is triturated with 100 milliliters of absolute ethanol, giving 30.6 grams of product .(78 percent). Recrystallization from a large volume of methanol gives colorless platelets of fl-ethylamino-u-hydroxypropionaldehyde hydrochloride [C H NHCH CH (OH) CHO HCl] melting point 153 degrees centigrade with decomposition. AnaL-Calcd. for C H ClNO C, 39.09; H, 7.88;

. 4 c1; 23.08; N, 9.12. Found: c, 39.25; H, 7.68; ct, 22.84; N,8.97.

ExampleZ A solution of 219.5 grams (296 milliliters or three moles) of n-butylamine, 146 grams (one mole) of unfiepoxypropionaldehyde diethyl acetal and five milliliters of methanol is allowed to stand overnight and is then heated under reflux for two hours. The excess n-butylamine is removed in vacuo on a steam bath and the residue distilled in vacuo through a seven-inch, helicespacked column. There is obtained 177.9 grams (8.1 percent) of {Ln-butylamino-a-hydroxypropionaldehyde diethylacetal [nC H NHCl-I CH(OH)CH(OC H as a colorless liquid boiling at 138 degrees centigrade at twelve millimeters pressure or at 107 degrees centigrade at 1.8 millimeters pressure n l.4413.

AnaL-Calcd. for C H NO C, 60.24; H, 11.49; N, 6.39. Found: C, 59.86; H, 11.22; N, 6.30.

To 45.1 grams of fi-n-butylamino-a-hydroxypropionaldehyde diethylacetal is added a solution of 22.36 milliliters of concentrated hydrochloric acid in 60.32 milliliters of water. The resulting solution is heated under reflux, using an air condenser, for 45 minutes. The orange solution is allowed to cool to room temperature (approximately one hour) and is thenconcentrated in vacuo on a water bath at forty degrees centigrade. The lighu cream, solid residue is triturated with 150 milliliters of acetone to give a colorless solid which darkens at about 142 degrees centigrade and finally decomposes at 180 degrees centigrade; weight 32.5 grams- (87 percent). Recrystallization of this solid from methanol gives fl-n-' butylamino a hydroxypropionalclehyde hydrochloride [nC H NHCH CHOl-ICHO-HCll as a colorless product decomposing at 183 degrees centigrade.

Anwl.--Calcd. for C H CINO C, 46.28; H, 8.88; N, 7.71; Cl, 19.52. Found: C, 46.38; H, 9.06; N, 7.43; CI, 19.23.

Example 3 the orange-colored reaction mixture is heated on the steam bath until all low-boiling material has distilled.

' The las't'traces are removed under a pressure of approximately twenty millimeters. The residual material is distilled under reduced pressure through a ten-inch Vigreux column. The B-diethylarnino-a-hydroxypropiom aldehyde diethylacetal boiling point 82-95 degrees centigrade at 0.50 millimeter pressure, is collected as a colorless liquid in a yield of 2459 grams (92 percent); 11 1.4334.

Anal.-Calcd. for C I-1 N0 2 C, 60.24; H, 11.49; N, 6.39. Found: C, 59.96; H, 11.44; N, 6.47.

In a five-liter, three-necked flask fitted with dropping funnel, mechanical stirrer and reflux condenser is prepared a solution of 559 grams concentrated hydrochloric acid (37 percent) and 1508 milliliters deionized water. To the well-stirred acid solution is added quite rapidly through the dropping funnel 1128 grams (5.15 moles) fi-diethylaminowhydroxypropionaldehyde diethylacetal. The mixture warms on addition of the acetal. The mixture is stirred at room temperature for thirty minutes and then for two hours at steam-bath temperature. The reaction mixture, while stirring continuously, is concen- (fifty percent). T This material, on recrystallization from 1750 milliliters ethyl alcohol, gives pale creamto white crystalline material. The fi-diethylamino-d-hydroxypropionaldehyde hydrochloride melting point 132-133 degrees centigrade, in this purified form is obtained in a yield of 388 grams (41 percent).

AnaL-Calcd. for CqHmClNOgI C, 46.28; H, 8.88; Cl, 19.52. Found: C, 46.26; H, 8.55; Cl, 19.45.

Example 4 In a 500-milliliter flask fitted with reflux condenser is prepared a cold solution of 22.5 grams (0.50 mole) dimethylamine in 200 milliliters of methanol. To the chilled solution is added 73 grams (0.50 mole) a43- epoxypropionaldehyde diethylacetal. The reaction mixture is allowed to stand in an ice bath for one hour, at room temperature for three hours, and .then heated under reflux for one hour. The methanol is distilled on the steam bath, leaving an orange oil which is distilled under reduced pressure through an eight-inch, glass-helicepacked column. The fl-dimethylamino-u-hydroxypropionaldehyde diethylacetal product, boiling point 100-101 degrees centrigrade at twelve millimeters pressure, is collected as a colorless oil; yield seventy grams'(73 percent); n 1.4292.

AnaL-Calcd. for C H NO C, 56.51; H, 11.07; N,

7.32. Found: C, 56.43; H, 11.24; N, 7.39.

In a SOD-milliliter flask is prepared a solution of 57.3 grams (0.30 mole) fi-dimethylaminda-hydroxypropionaldehyde diethylacetal and 150 milliliters of ten percent aqueous hydrochloric acid. The solution, after heating on the steam bath for two hours, is concentrated under reduced pressure. The amber residual gum is crystallized from a mixture of 125 milliliters of ethyl alcohol and 125 milliliters of ethyl acetate. The product, melting point 117-1185 degrees centigrade, is collected in a yield of 32 grams (69 percent). This material, after purification by decolorizing charcoal treatment and recrystallizing three times from 1:1 mixture of ethyl alcohol and ethyl acetate, has a melting point of 121.5- 123.5 degrees centigrade. The yield of purified p-dimethylamino-a-hydroxypropionaldehyde hydrochloride [(CH NCH CH(OH) CHO HCl] is eighteen grams (39 percent).

Anal.-Calcd. for C5H12CINO2I C, 39.09; H, 7.88; CI, 23.08. Found: C, 39.10; H, 7.94; Cl, 22.97.

Examples 5 and 6 To a solution of fifty milliliters (0.404 mole) of 25 percent methylamine solution in fifty milliliters of methanol is added dropwise over the course of. about fifteen minutes. 76.0 grams (0.52 mole) of u,;3-epoxypropionaldehyde diethylacetal. During this addition an exothermic reaction takes place and the temperature rises to 55 degrees centigrade. casionally in a pan of water to prevent the temperature going above this point. When the addition is complete the addition funnel is rinsed with an additional ten milliliters of methanol and the solution is allowed to stand overnight. The solution is heated under reflux for two hours and then concentrated under reduced pressure on a steam bath. The colorless residue is distilled under reduced pressure through a seven-inch column packed with glass helices. The first fraction boils at 110 degrees centigrade at thirteen millimeters pressure and solidifies in the condenser; Weight, 13.2 grams (14.4 percent). This fraction is fi-methylamino-a-hydroxypropionaldehyde diethylacetal [CH NHCH CH(OH)CH(OC H -Up0n recrystallization from Skellysolve B (mixture of.

AnaL-Calcd. for 0,11 ,810,: 0, 54.21.; H, 10.80; N,

7.90. Found: C, 54.01; H, 10.47; N, 7.82.

The flask is cooled oc- The second fraction consists of an almost colorless liquid boiling at degrees centigrade at 0.6 millimeter" pressure; weight 66.2 grams (79 percent); 11 1.4460. This fraction is the his compound; N,N-di-('y,'y-diethoxyfi-hydroxypropyl)-methylamine.

Anal.-Calcd. for C H NO C, 55.70; H, 10.28; N, 4.33. Found: C, 55.65, 55.97; H, 10.20, 10.46; N, 4.25, 4.56.

The foregoing reaction can be represented by the equation o-ontcnomoctmn OI-I3N1ICH2CH(OH)CH(OC2H5)2 (CQH O):CHCH(OH)GHzN(0H )CH CH(OH)'CH(OC2Hs)1 To 5.2 grams of N,N-di-('y,' -diethoxy-fi-hydroxypropyl)methylamine is added dilute hydrochloric acid (five. milliliters concentrated hydrochloric acid diluted with water to fifty milliliters) and the solution is allowed to stand for three days. The solution is concentrated under reduced pressure in a water bath below forty degrees centigrade and the colorless residue is transferred to a crystallizing dish and allowed to stand over concentrated sulfuric acid in a vacuum desiccator. for some time and then over potassium hydroxide. The residue is triturated with acetone until completelysolid. The N,N di (B hydroxy B 4 formylethyl) methylamine hydrochloride 146 grams (1.0 mole) u,fl-epoxypropionaldehyde diethyl acetal and three milliliters methanol. The solution is heated on the steam bath for seven hours and then al lowed to stand at room temperature overnight. The reaction mixture is heated on the steam bath under reduced pressure until all low boiling material has been removed. The residual oil is distilled under reduced pressure through a ten-inch, glass-helices packed column. The fi-diisopropylamino-a-hydroxypropionaldehyde diethylacetal l [(CH CH] NCH CH(OH)CH(OC H boiling point 84-88 degrees centigrade at 0.5 millimeter pressure, is collected as a pale yellow oil in a Anal.Calcd. for C H NO 5 C, 63.12; H, 11.82; N, 5.66. Found: C, 63.89; H, 11.71; N, 5.63.

In a ZOO-milliliter, three-necked, round-bottomed flask fitted with mechanical stirrer andreflux condenser is pre-, pared a solution of 37 grams (0.15 mole) fl-diisopr opylaimino-a-hydroxypropionaldehyde diethylacetal and sixty f grams ten percent hydrochloric acid. The solution after, heating and stirring on the steam bath for fifteen minutes, 1 begins t b il- Ifh so ion is stirred; tlsatss mau the steambathfor fourandone-half hours and then concentrated under reduced-pressure. The residual gum is dried with toluene, thendissolvedin a mixture of 100 milliliters ethyl alcohol-,200 milliliters ethyl acetate and 200' milliliters ether. and the solution cooled. The crystalline material (A) which separates is filtered. The filtrate is concentrated on the steam bath under reduced pressure and the residual gum, aft-er drying, is warmed on the steam bath with acetone. The white crystalline material (B) which separates is collected by filtration. After standing four to five hours; the acetone solution gives a third crop of crystals (C). The yield of crop (A), melting-point 215 degrees centigrade, is 2.0 grams, of (B), melting point 183-187 degrees centigrade, is 5.0 grams, and of (C), melting-point 175-177 degrees centigrade, is 4.5 grams. Crop (A) gives no depression of melting point with diisopropylamine hydrochloride. On combining crops (B) and (C) and recrystallizing twice from methanol and ether the product, melting point 196-198 degrees centigradc, weighs 3.8 grams (twelve percent). Infrared analysis shows the compound to be 8- diisopropylamino o -hydroxypropionaldehyde hydrochloride, (CH CH1 --'NCH CH(OH)CHO HCl, dimer.

Anal-salad. forC H ClNO C, 51.54; H, 9.61; N, 6.68; Cl, 16.91. Found: c, 51.69; H, 9.61; N, 6.69; or, 16.80.

From the residual filtrates is isolated a small amount of material which one Fischer-Johns block shows the following'changes on heating. At 120-130 degrees centigrade the material begins to color; at 150-160 degrees centigrade new crystals seem to form, and at 210-220 degrees centigradedefinite' melting takes place. Infrared analysis shows this material to be B-diisopropylamino-orhydroxypropionaldehyde hydrochloride,

monomer. I I

A'nd L-Calcdhfo'r C I-I ClNO C, 51.54; H, 9.61; N, 6.68, CI, 16.91. Found: C, 51.43; H, 9.34; N, 6.52; C1, 1659.

Example 8 A solution of 16.5 grams (0.05) mole of p-di-n-hexylamino-whydroxypropionaldehyde diethylacetal (obtained by reaction of di-n-hexylamine and a,B-epoxypropionaldehyde diethylacetal) and 500 milliliters of 0.1 normal hydrochloric acidis prepared. The clear colorless solution is allowed to standat room temperature for one week and then warmed on the steam bath for two hours. The solution is concentratedunder reduced pressure at forty to-sixty degreescentigrade. The pale-yellow, gurumy, solid residue is dissolved in 150 milliliters ethyl alcohol and the alcoholic solutiondiluted with 450 millilitersethyl acetate and 750 milliliters ether. After chilling in a Dry Ice chest, five grams of white crystalline material-is isolated. The di-n-hexylamino-a-hydroxypropionaldehyde hydrochloride,

[CH (CH 1 NC1-I CH(OH)CHO -HC1 after recrystallization from 55 milliliters ethyl alcohol and 400 milliliters ether, weighs three grams (twenty To 43.8 grams (0.200 mole) of p-diethylamino-ahydroxypropionaldehyde diethylacetal in a one-necked flask fittedwith an air condenser surmounted by a calcium chloride dryin tube is'added, with swirling, 20.4

rams (0.206 mole) or acetic anhydride. An exothermic reactiontakes place with'the reactionmixture warm ingto ninetyde rees;eentigradea During-this time the colorof the reactionmixture'changes to a yellow-brown.

The reaction mixture is allowed to cool to room tern perature over the course of about one-half hour and is then poured into 200 milliliters of ice-water. To the aqueous solution obtained is added seventeen grams of sodium bicarbonate, the mixture stirred well and extracted with ether. To the aqueous layer is added an additional ten grams of sodium bicarbonate and this layer again extracted twice with 150-milliliter portions of ether. The combined ethereal extracts are dried over anhydrous magnesium sulfate, the ether removed and the residue distilled in vacuo through a seven-inch column packed with glass helices. There is obtained 37.1 grams (71- percent) of,e-diethylarnino-rx-acetoxypropionaldehyde diethylacetal t c np ucn cmococnpcmoc n yn as a colorless liquid boiling at -106 degrees centi-' grade at 2.5 millimeters pressure; 1.4281.

acetoxypropionaldehyde diethylacetal is added a solution of 28.2 milliliters of concentrated hydrochloric acid and 56.4 milliliters of water. The temperature rises to 55 degrees centigrade. The colorless solution is allowed to stand overnight, and is then evaporated to dryness in vacuo at twenty millimeters pressure on a Water bath at sixty degrees centigrade. The yellow, viscous, oily residue is triturated' with 100 milliliters of acetone and al lowed to stand for several hours until crystallization is complete and the material in the flask is completely" solid. The material is filtered and washed with anhydrous ether; weight 18.3 grams. However, this" product is B-diethyla'mino-a-hydroxypropionaldehyde hydrochlo ride [(C H NCH CH(OH)CHO-HCl] dimer indicating that the acetoxy group is also cleaved during the foregoing hydrolysis process.

Example 10 [CH (CH NCH CH(OH)CH(OC H is 347 grams (84 percent); 11 1.4376.

Anal.-Calcd. for C H NO C, 65.41; H, 12.08; N,

5.09. Found: C, 66.03; H, 12.00; N, 5.68.

A solution of 27.5 grams (0.10 mole) of B-di-n-butylamino-whydroxypropionaldehyde diethylacetal in 82.5 milliliters of dilute hydrochloric acid (27.5 millilitersof concentrated hydrochloric acid and 55 milliliters of water) is prepared. The temperature of the solution rises to fifty degrees centrigrade. The pink solution is allowed to stand at room'temperature overnight and is then concentrated at sixty to seventy degrees Centigrade under re duced pressure. The residual gum is dissolvedinhot acetone and the solution then diluted with about onethird of its volume with ether. The White material which crystallizes after chilling in the refrigerator is filtered and dried in vacuo. The yield is 9.0 grams (forty percent); melting point 164.5- degrees centigrade (de'comipoSition). Recrystallization of the fi-di-n-butylamino-whydroxypropionaldehyde hydrochloride [CH3 CH NCH CH CH) CHO HCl product from a mixture of ethyl alcohol and ethyl acetate A yellow liquid, boiling 9 provides product melting at 179-180 degrees centigrade (decomposition). According to infrared analysis the product is a dimer.

Anal.-Calcd. for c,,H,,No,-Hc1; C, 55.56; H, 10.17; N, 5.89; Cl, 14.91. Found: C, 55.30; H, 9.94; N, 5.69; CI, 14.16.

Example 11 To a solution of 150 milliliters (approximately five equivalents) of ammonium hydroxide solution and 300 milliliters of methanol is added rapidly 73 grams (0.5 mole) of afi-epoXypropionaldehyde diethylacetal. The solution is stirred and heated at 50 to 55 degrees centigrade for two hours and then allowed to stand overnight. The excess methanol and ammonium hydroxide are removed by distillation through a short Vigrenx column, first at atmospheric pressure and then under reduced pressure on a steam bath. The residue is distilled through a seven-inch, helices-packed column. There is obtained a colorless viscous liquid boiling at 116 degrees centigrade at thirteen millimeters pressure and a rather large residue of higher boiling product. The lower boiling distillate solidifies on standing to a glassy solid which, upon recrystallization from Skellysolve B (mixture of hexanes), gives colorless asbestos-like needles of fl-amino-u-hydroxypropionaldehyde diethylacetal melting point 41 degrees Centigrade. The higher boiling residue is subjected to distillation through a three-inch Vigreux column. There is obtained a yellow liquid boiling at 170-171 degrees centigrade at 1.3 millimeters pressure which is di-(yyy-diethoxy-fi-hydroxypropyl)-amine Hydrolysis of this acetal with dilute aqueous hydrochloric acid according to the usual procedure described previously, e. g. in Examples and 6, provides di-(fi-hydroxy- /3-formylethyl)-amine hydrochloride [OHCCH OH) CH NHCH CH OH) CHO HCl] product.

Example 12 in a few days. The product decomposes when distillation in vacuo is attempted.

Treatment of freshly prepared B-diethylamino-a-hydroxypropionaldehyde free base dissolved in ethyl alcohol with the theoretical amount of acetic acid provides fi-diethylaminmwhydroxypropionaldehyde acetate In the same manner ,G-diethylamino-u-hydroxypropionaldehyde propionate, oxalate, benzoate, cyclopentylpropionate, phenylacetate, valerate, etc., salts are prepared by reaction of the free base with the appropriate acid.

Example 13 By following the procedures of Examples 1-12, the hydrochloride, hydrobromide, hydriodide, sulfate, phos phate, formate, acetate, benzoate, trichloroacetate, citrate, maleate, aand B-phenylpropionate, aand fi-cyclopentylpropionate, furoate, etc., salts of fi-n-butylar'nino-ahydroxy-n-hexaldehyde, 8-ethylamino-m-hydroxy-isobntyraldehyde, fl-n-octylammoa-hydroxypropionaldehyde, B- methylethylamino oz hydroxypropionaldehyde, fi-di-noctylamino 0c hydroxypropionaldehyde, ,6 diisohexylamino a hydroxypropionaldehyde, B ethylamino-u-hydroxy a methyl-n-butyraldehyde, fi-diethylamino-ac-hydroxy 0c methylisovaleraldehyde, fi-isooctylamino-a-hydroxypropionaldehydc, [3 n heptylamino u hydroxy-nbutyraldehyde, fi-diisopentylamino-a-hydroxypropionaldehyde, etc., are prepared.

It is to be understood that the invention is not to be limited to the exact details of operation or exact compounds shown and described, as obvious modifications and equivalents will be apparent to one skilled in the art, and the invention is therefore to be limited only by the scope of the appended claims.

We claim:

1. Compounds of the formula R2 wherein R is selected from the group consisting of hydrogen and alkyl, R is selected from the group consisting of alkyl and B-formyl-fi-hydroxy-(lower-alkylene), loweralkylene contains from two to five carbon atoms, inclusive, alkyl contains from one to eight carbon atoms, inclusive, and HX is an acid having a pK value less than five.

2. 5 alkylamino 0t hydroxypropionaldehyde mineral acid addition compounds of the formula wherein alkyl contains from one to eight carbonatoms, inclusive.

3. ,8-dialkylamino-a-hydroxypropionaldehyde mineral acid addition compounds of the formula (III) OH allkyl HC-tJH-CHg-N-Inlneral acid kyl wherein lower-alkyl contains from one to :four carbon atoms, inclusive.

6. B-diethylamino oz hydroxypropionaldehyde hydrochloride.

7. fl-diisopropylamino a hydroxypropionaldehyde hydrochloride.

8. ,B-dimethylamino-a-hydroxypropionaldehyde hydrochloride.

9. fl ethylamino-u-hydroxypropionaldehyde hydrochloride.

10. fi-n-butylamino-a-hydroxypropionaldehyde hydrochloride. dimethyl References Cited in the tile of this patent UNITED STATES PATENTS 1,824,676,

Mannich Sept. 22, 1931 UNITED STATES PATENT OFFICE Certificate of Correction Patent No. 2,875,248 February 24, 1959 John B. Wright et al.

It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Columns 1 and 2, Table 1, first column thereof, eighth item, left-hand portion, for (n-C H 2N-- read -(n-G H N- same table, third column, in the heading thereto, for Newcastle s Virus read --Newcastles Virus-; column 3, line 6, for oxali aid read -oxalic acid-; line 59, for 0.512 mole) read (0.512 mole); column 4, line 54, for [G H read (O H column 5, line 5, for [(C H NCH read [(G H -NGH line 26, for centri ade read -centigrade-; column 7, line 23, for [(CH CH] NOH read H GH] -NOH column 8 line 62, for centrigrade read --centigrade-; column 9, line 26, for 501-1) CH--(O H read (OH) GH-(OO H column 10, line 71, strike out dimethyl.

Signed and sealed this 28th day of July 1959.

Attest: l

KARL H. AXLINE, ROBERT C. WATSON,

A'ttes'ting "O'yficer. Uomnnissz'oner of Patents. 

1. COMPOUNDS OF THE FORMULA 